Chiral Molecular Recognition in a Tripeptide Benzylviologen Cyclophane Host

A cationic chiral cyclophane was synthesized and studied as a host for chiral and racemic π-donor molecules. The cyclophane host has a rigid binding cavity flanked by ( S )-(valine-leucine-alanine) and N, N ‘-dibenzyl-4,4‘-bipyridinium subunits, which allow for hydrogen-bonding and π-stacking interactions with included aromatic guest molecules. 1 H NMR binding titrations were performed with several different pharmaceutically interesting guest molecules including β-blockers, NSAIDs, and amino acids and amino acid derivatives. The host−guest complexation constants were generally small for neutral and cationic guests (0−39 M - 1 at 20 °C in water/acetone mixtures). However, a ( R )/( S ) enantioselectivity ratio of 13 ± 5 was found for DOPA, a strongly π-donating cationic guest. Two-dimensional NOESY 1 H NMR spectra confirm that ( R )-DOPA binds inside the cavity of the host and that there is no measurable interaction of the cavity with ( S )-DOPA under the same conditions.